DESeq2 Multifactor Analysis Final Project

Goals for DGE Analysis

The goals for this analysis are to investigate how the gene expression changes based on the mouse model, genotype within the mouse model, and age. Questions to answer: -What genes are differentially expressed due to Mouse Model Alone? -How does aging affect gene expression within each mouse model? -How does the genotype within each mouse model affect gene expression at different time points?

Import experimental design matrix.

library(DESeq2)
library(pheatmap)
library(dplyr)
library(dendextend)

design_matrix<-read.table('/Users/danielaquijano/Documents/GitHub/Transcriptomics-Final-Project-/source_files/Experimental_Design.csv',sep=',',header=TRUE)

rownames(design_matrix)<-design_matrix$Sample
design_matrix$Sample<-NULL

design_matrix

Import matrix containing the counts for all samples. These counts represent the forward strand counts since this was a stranded library.

counts_matrix<-read.table("/Users/danielaquijano/Documents/GitHub/Transcriptomics-Final-Project-/Count_Tables/allcounts.csv",sep=',',header=TRUE)

counts_matrix

Because the numbers after the dot in the ensembl IDs represent versions of genes in certain annotations, we can remove these to more easily conduct our differential gene expression analysis.

counts_matrix$V1<-gsub("\\..*","",counts_matrix$V1)

counts_matrix

rownames(counts_matrix)<-counts_matrix$V1
counts_matrix$V1<-NULL

We need to sort the counts_matrix as well as our experimental design matrix in order to run DESEQ2

counts_matrix<-counts_matrix[,order(colnames(counts_matrix))]

counts_matrix

design_matrix<-design_matrix[order(rownames(design_matrix)),]

design_matrix

dds <- DESeqDataSetFromMatrix(countData = counts_matrix,
                              colData = design_matrix,
                              design = ~ Genotype + Age+ Model)

Warning in DESeqDataSet(se, design = design, ignoreRank) :
  some variables in design formula are characters, converting to factors
  the design formula contains one or more numeric variables with integer values,
  specifying a model with increasing fold change for higher values.
  did you mean for this to be a factor? if so, first convert
  this variable to a factor using the factor() function
  the design formula contains one or more numeric variables that have mean or
  standard deviation larger than 5 (an arbitrary threshold to trigger this message).
  Including numeric variables with large mean can induce collinearity with the intercept.
  Users should center and scale numeric variables in the design to improve GLM convergence.

dds

class: DESeqDataSet 
dim: 46075 72 
metadata(1): version
assays(1): counts
rownames(46075): ENSMUSG00000000001 ENSMUSG00000000003 ... N_noFeature N_unmapped
rowData names(0):
colnames(72): SRR8512301 SRR8512302 ... SRR8512439 SRR8512440
colData names(3): Model Genotype Age

Remove genes with counts less than 10

keep <- rowSums(counts(dds)) >= 10
dds <- dds[keep,]

Run DESeq

dds <- DESeq(dds)

using pre-existing size factors
estimating dispersions
found already estimated dispersions, replacing these
gene-wise dispersion estimates
mean-dispersion relationship
final dispersion estimates
fitting model and testing
-- replacing outliers and refitting for 34 genes
-- DESeq argument 'minReplicatesForReplace' = 7 
-- original counts are preserved in counts(dds)
estimating dispersions
fitting model and testing

rawcounts.matrix <- counts(dds,normalized=F)
normalizedcounts.matrix <- counts(dds,normalized=T)

vst_dds <- vst(dds)
dists <- dist(t(assay(vst_dds)))

dists

TO DO: *****Label samples

dendogram<-plot(hclust(dists),cex=0.6)

labels(dendogram)

character(0)

Trying to rename labels….

dend <- dists %>%  hclust %>% as.dendrogram
dend %>% set("labels", c(rep('rtg4510',26),rep('J20',42),rep('rtg4510',4))) %>% set("labels_cex", 0.5) %>% plot

`

*** Add title, make graph cute (size bigger) Capitalize group

plotPCA(vst_dds,intgroup=c("Model","Genotype","Age"))

Obtain results based on different contrasts

What genes are differentially expressed due to Mouse Model Alone?

res_1 <- results(dds, contrast = c("Model","rtg4510","J20"))

res1_ordered <- res_1[order(res_1$pvalue),] 
head(res1_ordered,200)

log2 fold change (MLE): Model rtg4510 vs J20 
Wald test p-value: Model rtg4510 vs J20 
DataFrame with 200 rows and 6 columns
                    baseMean log2FoldChange     lfcSE      stat       pvalue         padj
                   <numeric>      <numeric> <numeric> <numeric>    <numeric>    <numeric>
ENSMUSG00000005677   328.896        8.26452 0.2131736   38.7689            0            0
ENSMUSG00000005983   246.217        3.72650 0.0742760   50.1710            0            0
ENSMUSG00000006638   132.773        3.38797 0.0803164   42.1827            0            0
ENSMUSG00000011658   445.560        2.93788 0.0712441   41.2368            0            0
ENSMUSG00000012126   246.792        3.01331 0.0779703   38.6469            0            0
...                      ...            ...       ...       ...          ...          ...
ENSMUSG00000097712   74.2415        6.04755 0.2101826   28.7728 4.69241e-182 5.54399e-180
ENSMUSG00000064368 6615.3200        4.05861 0.1414058   28.7019 3.61766e-181 4.25250e-179
ENSMUSG00000097537   54.7733        4.34720 0.1519897   28.6020 6.35047e-180 7.42717e-178
ENSMUSG00000027536   65.8562        4.51330 0.1578768   28.5875 9.60648e-180 1.11788e-177
ENSMUSG00000032182  358.6079        1.49445 0.0522791   28.5861 1.00125e-179 1.15930e-177

Filter the res1_ordered byp value to obtain only those genes with p value less than 0.05

#Filter Differentially Expressed Genes by p value 0.05
res1_ordered_filtered <- res1_ordered[res1_ordered$pvalue<0.05,]

See how many genes have p value equals to zero

res1_ordered_filtered_2 <- res1_ordered[res1_ordered$pvalue==0,]

Genes with pvalue==0

res1_ordered_filtered_2

log2 fold change (MLE): Model rtg4510 vs J20 
Wald test p-value: Model rtg4510 vs J20 
DataFrame with 100 rows and 6 columns
                      baseMean log2FoldChange     lfcSE      stat    pvalue      padj
                     <numeric>      <numeric> <numeric> <numeric> <numeric> <numeric>
ENSMUSG00000005677     328.896        8.26452 0.2131736   38.7689         0         0
ENSMUSG00000005983     246.217        3.72650 0.0742760   50.1710         0         0
ENSMUSG00000006638     132.773        3.38797 0.0803164   42.1827         0         0
ENSMUSG00000011658     445.560        2.93788 0.0712441   41.2368         0         0
ENSMUSG00000012126     246.792        3.01331 0.0779703   38.6469         0         0
...                        ...            ...       ...       ...       ...       ...
ENSMUSG00000101840     364.904        8.02583 0.1907698   42.0708         0         0
ENSMUSG00000103309     312.482        6.02111 0.1332254   45.1949         0         0
ENSMUSG00000104002     373.763        8.22813 0.1854888   44.3592         0         0
ENSMUSG00000104548     139.080        5.45187 0.1411758   38.6176         0         0
N_noFeature        6513000.933        3.42151 0.0419054   81.6485         0         0

Genes with pvalue<0.05

res1_ordered_filtered

log2 fold change (MLE): Model rtg4510 vs J20 
Wald test p-value: Model rtg4510 vs J20 
DataFrame with 13919 rows and 6 columns
                      baseMean log2FoldChange     lfcSE      stat    pvalue      padj
                     <numeric>      <numeric> <numeric> <numeric> <numeric> <numeric>
ENSMUSG00000005677     328.896        8.26452 0.2131736   38.7689         0         0
ENSMUSG00000005983     246.217        3.72650 0.0742760   50.1710         0         0
ENSMUSG00000006638     132.773        3.38797 0.0803164   42.1827         0         0
ENSMUSG00000011658     445.560        2.93788 0.0712441   41.2368         0         0
ENSMUSG00000012126     246.792        3.01331 0.0779703   38.6469         0         0
...                        ...            ...       ...       ...       ...       ...
ENSMUSG00000030149    0.640484      -1.942038 0.9893484  -1.96295 0.0496523 0.0826361
ENSMUSG00000102780    6.648616      -0.667267 0.3399851  -1.96264 0.0496886 0.0826905
ENSMUSG00000044092    4.705449       0.609800 0.3107387   1.96242 0.0497135 0.0827261
ENSMUSG00000020444 1079.863558       0.129839 0.0662114   1.96098 0.0498818 0.0830001
ENSMUSG00000098973 3353.343963      -0.380913 0.1942993  -1.96044 0.0499442 0.0830979

-How does aging affect gene expression within each mouse model?

res_2 <- results(dds, contrast = c("Age","2","8"))

?results

-How does the genotype within each mouse model affect gene expression at different time points?

#GO-Term Enrichment

Install Mouse annotation library:

BiocManager::install("org.Mm.eg.db")

'getOption("repos")' replaces Bioconductor standard repositories, see '?repositories' for
details

replacement repositories:
    CRAN: https://cran.rstudio.com/

Bioconductor version 3.14 (BiocManager 1.30.16), R 4.1.2 (2021-11-01)
Installing package(s) 'org.Mm.eg.db'
installing the source package 'org.Mm.eg.db'

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** help
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** testing if installed package keeps a record of temporary installation path
* DONE (org.Mm.eg.db)

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  'Seurat', 'SeuratObject', 'shadowtext', 'testthat'

Update all/some/none? [a/s/n]: 

a

also installing the dependencies 'sp', 'rgeos'

  There are binary versions available but the source versions are later:

Yes

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The downloaded binary packages are in
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* installing *source* package ‘SeuratObject’ ...
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    #pragma clang diagnostic pop
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    #pragma clang diagnostic pop
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                             ^
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    #pragma clang diagnostic pop
                             ^
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/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
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/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
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In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:27:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/OrderingMethods:71:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RcppExports.cpp:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:29:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/SparseCholesky:43:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RcppExports.cpp:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:32:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/SparseQR:34:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RcppExports.cpp:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:33:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/IterativeLinearSolvers:46:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RcppExports.cpp:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:32:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/CholmodSupport:45:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RcppExports.cpp:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:35:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/KroneckerProduct:34:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/../../Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RcppExports.cpp:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:39:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/Polynomials:135:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/../../Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RcppExports.cpp:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:40:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/SparseExtra:51:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/../../Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
18 warnings generated.

clang++ -mmacosx-version-min=10.13 -std=gnu++14 -I"/Library/Frameworks/R.framework/Resources/include" -DNDEBUG  -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/Rcpp/include' -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include' -I/usr/local/include   -fPIC  -Wall -g -O2  -c data_manipulation.cpp -o data_manipulation.o

In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Core:540:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:2:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/LU:47:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:3:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Cholesky:12:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Jacobi:29:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:3:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Cholesky:43:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/QR:15:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Householder:27:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/QR:48:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:5:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/SVD:48:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:6:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Geometry:58:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:7:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Eigenvalues:58:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:26:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/SparseCore:66:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:27:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/OrderingMethods:71:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:29:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/SparseCholesky:43:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:32:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/SparseQR:34:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:33:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/IterativeLinearSolvers:46:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:32:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/CholmodSupport:45:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:35:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/KroneckerProduct:34:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/../../Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:39:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/Polynomials:135:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/../../Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:40:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/SparseExtra:51:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/../../Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
18 warnings generated.

clang -mmacosx-version-min=10.13 -I"/Library/Frameworks/R.framework/Resources/include" -DNDEBUG  -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/Rcpp/include' -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include' -I/usr/local/include   -fPIC  -Wall -g -O2  -c valid_pointer.c -o valid_pointer.o
clang++ -mmacosx-version-min=10.13 -std=gnu++14 -dynamiclib -Wl,-headerpad_max_install_names -undefined dynamic_lookup -single_module -multiply_defined suppress -L/Library/Frameworks/R.framework/Resources/lib -L/usr/local/lib -o SeuratObject.so RcppExports.o data_manipulation.o valid_pointer.o -F/Library/Frameworks/R.framework/.. -framework R -Wl,-framework -Wl,CoreFoundation

ld: warning: text-based stub file /System/Library/Frameworks//CoreFoundation.framework/CoreFoundation.tbd and library file /System/Library/Frameworks//CoreFoundation.framework/CoreFoundation are out of sync. Falling back to library file for linking.
installing to /Library/Frameworks/R.framework/Versions/4.1/Resources/library/00LOCK-SeuratObject/00new/SeuratObject/libs
** R
** data
*** moving datasets to lazyload DB
** byte-compile and prepare package for lazy loading
** help
*** installing help indices
** building package indices
** testing if installed package can be loaded from temporary location
** checking absolute paths in shared objects and dynamic libraries
** testing if installed package can be loaded from final location
** testing if installed package keeps a record of temporary installation path
* DONE (SeuratObject)
* installing *source* package ‘Seurat’ ...
** package ‘Seurat’ successfully unpacked and MD5 sums checked
** using staged installation
** libs

clang++ -mmacosx-version-min=10.13 -std=gnu++11 -I"/Library/Frameworks/R.framework/Resources/include" -DNDEBUG  -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/Rcpp/include' -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include' -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppProgress/include' -I/usr/local/include   -fPIC  -Wall -g -O2  -c ModularityOptimizer.cpp -o ModularityOptimizer.o

ModularityOptimizer.cpp:762:7: warning: unused variable 'n2_max' [-Wunused-variable]
  int n2_max = *std::max_element(node2.cbegin(), node2.cend());
      ^
ModularityOptimizer.cpp:761:7: warning: unused variable 'n1_max' [-Wunused-variable]
  int n1_max = *std::max_element(node1.cbegin(), node1.cend());
      ^
2 warnings generated.

clang++ -mmacosx-version-min=10.13 -std=gnu++11 -I"/Library/Frameworks/R.framework/Resources/include" -DNDEBUG  -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/Rcpp/include' -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include' -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppProgress/include' -I/usr/local/include   -fPIC  -Wall -g -O2  -c RModularityOptimizer.cpp -o RModularityOptimizer.o

In file included from RModularityOptimizer.cpp:9:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Core:540:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RModularityOptimizer.cpp:9:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:2:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/LU:47:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RModularityOptimizer.cpp:9:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:3:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Cholesky:12:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Jacobi:29:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RModularityOptimizer.cpp:9:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:3:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Cholesky:43:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RModularityOptimizer.cpp:9:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/QR:15:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Householder:27:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RModularityOptimizer.cpp:9:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/QR:48:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RModularityOptimizer.cpp:9:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:5:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/SVD:48:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RModularityOptimizer.cpp:9:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:6:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Geometry:58:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RModularityOptimizer.cpp:9:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:7:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Eigenvalues:58:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RModularityOptimizer.cpp:9:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:26:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/SparseCore:66:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RModularityOptimizer.cpp:9:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:27:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/OrderingMethods:71:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RModularityOptimizer.cpp:9:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:29:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/SparseCholesky:43:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RModularityOptimizer.cpp:9:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:32:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/SparseQR:34:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RModularityOptimizer.cpp:9:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:33:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/IterativeLinearSolvers:46:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RModularityOptimizer.cpp:9:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:32:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/CholmodSupport:45:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RModularityOptimizer.cpp:9:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:35:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/KroneckerProduct:34:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/../../Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RModularityOptimizer.cpp:9:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:39:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/Polynomials:135:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/../../Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RModularityOptimizer.cpp:9:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:40:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/SparseExtra:51:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/../../Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
18 warnings generated.

clang++ -mmacosx-version-min=10.13 -std=gnu++11 -I"/Library/Frameworks/R.framework/Resources/include" -DNDEBUG  -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/Rcpp/include' -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include' -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppProgress/include' -I/usr/local/include   -fPIC  -Wall -g -O2  -c RcppExports.cpp -o RcppExports.o

In file included from RcppExports.cpp:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Core:540:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RcppExports.cpp:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:2:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/LU:47:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RcppExports.cpp:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:3:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Cholesky:12:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Jacobi:29:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RcppExports.cpp:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:3:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Cholesky:43:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RcppExports.cpp:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/QR:15:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Householder:27:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RcppExports.cpp:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/QR:48:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RcppExports.cpp:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:5:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/SVD:48:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RcppExports.cpp:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:6:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Geometry:58:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RcppExports.cpp:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:7:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Eigenvalues:58:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RcppExports.cpp:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:26:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/SparseCore:66:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RcppExports.cpp:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:27:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/OrderingMethods:71:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RcppExports.cpp:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:29:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/SparseCholesky:43:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RcppExports.cpp:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:32:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/SparseQR:34:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RcppExports.cpp:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:33:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/IterativeLinearSolvers:46:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RcppExports.cpp:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:32:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/CholmodSupport:45:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RcppExports.cpp:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:35:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/KroneckerProduct:34:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/../../Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RcppExports.cpp:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:39:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/Polynomials:135:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/../../Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from RcppExports.cpp:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:40:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/SparseExtra:51:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/../../Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
18 warnings generated.

clang++ -mmacosx-version-min=10.13 -std=gnu++11 -I"/Library/Frameworks/R.framework/Resources/include" -DNDEBUG  -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/Rcpp/include' -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include' -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppProgress/include' -I/usr/local/include   -fPIC  -Wall -g -O2  -c data_manipulation.cpp -o data_manipulation.o

In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Core:540:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:2:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/LU:47:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:3:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Cholesky:12:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Jacobi:29:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:3:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Cholesky:43:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/QR:15:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Householder:27:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/QR:48:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:5:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/SVD:48:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:6:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Geometry:58:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:7:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Eigenvalues:58:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:26:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/SparseCore:66:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:27:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/OrderingMethods:71:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:29:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/SparseCholesky:43:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:32:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/SparseQR:34:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:33:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/IterativeLinearSolvers:46:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:32:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/CholmodSupport:45:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:35:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/KroneckerProduct:34:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/../../Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:39:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/Polynomials:135:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/../../Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from data_manipulation.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:40:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/SparseExtra:51:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/../../Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
18 warnings generated.

clang++ -mmacosx-version-min=10.13 -std=gnu++11 -I"/Library/Frameworks/R.framework/Resources/include" -DNDEBUG  -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/Rcpp/include' -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include' -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppProgress/include' -I/usr/local/include   -fPIC  -Wall -g -O2  -c fast_NN_dist.cpp -o fast_NN_dist.o
clang++ -mmacosx-version-min=10.13 -std=gnu++11 -I"/Library/Frameworks/R.framework/Resources/include" -DNDEBUG  -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/Rcpp/include' -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include' -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppProgress/include' -I/usr/local/include   -fPIC  -Wall -g -O2  -c integration.cpp -o integration.o

In file included from integration.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Core:540:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from integration.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:2:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/LU:47:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from integration.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:3:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Cholesky:12:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Jacobi:29:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from integration.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:3:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Cholesky:43:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from integration.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/QR:15:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Householder:27:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from integration.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/QR:48:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from integration.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:5:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/SVD:48:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from integration.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:6:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Geometry:58:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from integration.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:7:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Eigenvalues:58:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from integration.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:26:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/SparseCore:66:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from integration.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:27:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/OrderingMethods:71:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from integration.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:29:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/SparseCholesky:43:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from integration.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:32:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/SparseQR:34:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from integration.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:33:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/IterativeLinearSolvers:46:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from integration.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:32:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/CholmodSupport:45:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from integration.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:35:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/KroneckerProduct:34:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/../../Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from integration.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:39:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/Polynomials:135:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/../../Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from integration.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:40:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/SparseExtra:51:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/../../Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
18 warnings generated.

clang++ -mmacosx-version-min=10.13 -std=gnu++11 -I"/Library/Frameworks/R.framework/Resources/include" -DNDEBUG  -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/Rcpp/include' -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include' -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppProgress/include' -I/usr/local/include   -fPIC  -Wall -g -O2  -c snn.cpp -o snn.o

In file included from snn.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Core:540:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from snn.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:2:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/LU:47:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from snn.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:3:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Cholesky:12:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Jacobi:29:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from snn.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:3:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Cholesky:43:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from snn.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/QR:15:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Householder:27:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from snn.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:4:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/QR:48:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from snn.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:5:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/SVD:48:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from snn.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:6:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Geometry:58:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from snn.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:30:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:7:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Eigenvalues:58:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from snn.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:26:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/SparseCore:66:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from snn.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:27:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/OrderingMethods:71:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from snn.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:29:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/SparseCholesky:43:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from snn.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:32:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/SparseQR:34:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from snn.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:31:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Sparse:33:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/IterativeLinearSolvers:46:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from snn.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:32:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/CholmodSupport:45:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from snn.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:35:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/KroneckerProduct:34:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/../../Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from snn.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:39:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/Polynomials:135:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/../../Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
In file included from snn.cpp:1:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigen.h:25:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/RcppEigenForward.h:40:
In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/SparseExtra:51:
/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported/Eigen/../../Eigen/src/Core/util/ReenableStupidWarnings.h:14:30: warning: pragma diagnostic pop could not pop, no matching push [-Wunknown-pragmas]
    #pragma clang diagnostic pop
                             ^
18 warnings generated.

clang++ -mmacosx-version-min=10.13 -std=gnu++11 -I"/Library/Frameworks/R.framework/Resources/include" -DNDEBUG  -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/Rcpp/include' -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include' -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppProgress/include' -I/usr/local/include   -fPIC  -Wall -g -O2  -c stats.cpp -o stats.o
clang -mmacosx-version-min=10.13 -I"/Library/Frameworks/R.framework/Resources/include" -DNDEBUG  -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/Rcpp/include' -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include' -I'/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppProgress/include' -I/usr/local/include   -fPIC  -Wall -g -O2  -c valid_pointer.c -o valid_pointer.o
clang++ -mmacosx-version-min=10.13 -std=gnu++11 -dynamiclib -Wl,-headerpad_max_install_names -undefined dynamic_lookup -single_module -multiply_defined suppress -L/Library/Frameworks/R.framework/Resources/lib -L/usr/local/lib -o Seurat.so ModularityOptimizer.o RModularityOptimizer.o RcppExports.o data_manipulation.o fast_NN_dist.o integration.o snn.o stats.o valid_pointer.o -F/Library/Frameworks/R.framework/.. -framework R -Wl,-framework -Wl,CoreFoundation

ld: warning: text-based stub file /System/Library/Frameworks//CoreFoundation.framework/CoreFoundation.tbd and library file /System/Library/Frameworks//CoreFoundation.framework/CoreFoundation are out of sync. Falling back to library file for linking.
installing to /Library/Frameworks/R.framework/Versions/4.1/Resources/library/00LOCK-Seurat/00new/Seurat/libs
** R
** data
*** moving datasets to lazyload DB
** inst
** byte-compile and prepare package for lazy loading
** help
*** installing help indices
** building package indices
** testing if installed package can be loaded from temporary location
** checking absolute paths in shared objects and dynamic libraries
** testing if installed package can be loaded from final location
** testing if installed package keeps a record of temporary installation path
* DONE (Seurat)

The downloaded source packages are in
    '/private/var/folders/kz/671nytjx6wbb6qvvfpv7jwt00000gn/T/RtmpZsfRYg/downloaded_packages'

install.packages("devtools")

Error in install.packages : Updating loaded packages

devtools::install_github("stephenturner/annotables")

Skipping install of 'annotables' from a github remote, the SHA1 (631423c3) has not changed since last install.
  Use `force = TRUE` to force installation

install.packages("ggnewscale")

trying URL 'https://cran.rstudio.com/bin/macosx/contrib/4.1/ggnewscale_0.4.7.tgz'
Content type 'application/x-gzip' length 342566 bytes (334 KB)
==================================================
downloaded 334 KB

The downloaded binary packages are in
    /var/folders/kz/671nytjx6wbb6qvvfpv7jwt00000gn/T//Rtmp5PGlCM/downloaded_packages

library(biomaRt) #For conversion of transcript IDs to gene ID
library(annotables) #to retrieve grcm38 annotation for mouse genome
library(org.Mm.eg.db) #Mouse genome annotation
library(DOSE)
library(pathview)
library(clusterProfiler)
library(AnnotationHub) 
library(ensembldb)
library(tidyverse)
library(ggnewscale)

grcm38

res1_ordered

log2 fold change (MLE): Model rtg4510 vs J20 
Wald test p-value: Model rtg4510 vs J20 
DataFrame with 25644 rows and 6 columns
                      baseMean log2FoldChange     lfcSE         stat    pvalue      padj
                     <numeric>      <numeric> <numeric>    <numeric> <numeric> <numeric>
ENSMUSG00000005677     328.896        8.26452 0.2131736      38.7689         0         0
ENSMUSG00000005983     246.217        3.72650 0.0742760      50.1710         0         0
ENSMUSG00000006638     132.773        3.38797 0.0803164      42.1827         0         0
ENSMUSG00000011658     445.560        2.93788 0.0712441      41.2368         0         0
ENSMUSG00000012126     246.792        3.01331 0.0779703      38.6469         0         0
...                        ...            ...       ...          ...       ...       ...
ENSMUSG00000097946 2.66245e-01    2.25613e-04 1.1337219  1.99002e-04  0.999841        NA
ENSMUSG00000025422 1.29207e+04    7.45831e-06 0.0766118  9.73520e-05  0.999922  0.999922
ENSMUSG00000086026 1.25633e-01    5.73096e-05 2.1472359  2.66899e-05  0.999979        NA
ENSMUSG00000098630 1.22663e-01   -4.55876e-05 2.3745064 -1.91988e-05  0.999985        NA
ENSMUSG00000076596 0.00000e+00    0.00000e+00 0.0000000  0.00000e+00  1.000000        NA

idx <- grcm38$ensgene %in% rownames(res1_ordered)

ids <- grcm38[idx, ]

non_duplicates <- which(duplicated(ids$ensgene) == FALSE)

ids <- ids[non_duplicates, ]

res_ids <- inner_join(res1_ordered, ids, by=c("ensgene"="symbol")) 

ids

Because we have transcript IDs, we want ensembl ids in order to be able to conduct GO Term enrichment we need ensembl ID

In order to conduct the hypergeometric test on each set of differentially expressed genes we need to have two sets of genes: a background set, and a significant differentially expressed gene set. The background set will be comprised of all differentially expressed genes and the genes of interest will be those with significant p values (0.05).

We are using ‘ALL’ for ontology because we want to see all of the differentially expressed genes accross all categories.

## Use mouse genome 
ego <- enrichGO(gene = rownames(res1_ordered_filtered), 
                universe =ids$ensgene ,
                keyType = "ENSEMBL",
                OrgDb = org.Mm.eg.db, 
                ont = "ALL", 
                pAdjustMethod = "BH", 
                qvalueCutoff = 0.05, 
                readable = TRUE,
                pool=TRUE)
                
## Output results from GO analysis to a table
enriched_genes_res1 <- data.frame(ego)

enriched_genes_res1

dotplot(ego, showCategory=50)+theme(text = element_text(size = 1)) +scale_y_discrete(labels=function(x) str_wrap(x, width=40))

Scale for 'y' is already present. Adding another scale for 'y', which will replace the
existing scale.

OE_foldchanges <- res1_ordered_filtered$log2FoldChange
OE_foldchanges<-head(OE_foldchanges,50)

names(OE_foldchanges) <- rownames(head(res1_ordered_filtered,50))

cnetplot(ego, 
         categorySize="pvalue", 
         showCategory = 5, 
         foldChange=OE_foldchanges, 
         vertex.label.font=2)

Warning: ggrepel: 515 unlabeled data points (too many overlaps). Consider increasing max.overlaps